Wang et al Journal of Hematology & Oncology 2010, 3:30 http://www.jhoonline.org/content/3/1/30 CASE REPORT JOURNAL OF HEMATOLOGY & ONCOLOGY Open Access Cytostatic and anti-angiogenic effects of temsirolimus in refractory mantle cell lymphoma Li Wang1,2, Wen-Yu Shi1, Zhi-Yuan Wu3, Mariana Varna2,4, Ai-Hua Wang1, Li Zhou1, Li Chen1, Zhi-Xiang Shen1, He Lu2,4, Wei-Li Zhao1,2*, Anne Janin2,4* Abstract Mantle cell lymphoma (MCL) is a rare and aggressive type of B-cell non-Hodgkin’s lymphoma Patients become progressively refractory to conventional chemotherapy, and their prognosis is poor However, a 38% remission rate has been recently reported in refractory MCL treated with temsirolimus, a mTOR inhibitor Here we had the opportunity to study a case of refractory MCL who had tumor regression two months after temsirolimus treatment, and a progression-free survival of 10 months In this case, lymph node biopsies were performed before and six months after temsirolimus therapy Comparison of the two biopsies showed that temsirolimus inhibited tumor cell proliferation through cell cycle arrest, but did not induce any change in the number of apoptotic tumor cells Apart from this cytostatic effect, temsirolimus had an antiangiogenic effect with decrease of tumor microvessel density and of VEGF expression Moreover, numerous patchy, well-limited fibrotic areas, compatible with post-necrotic tissue repair, were found after 6-month temsirolimus therapy Thus, temsirolimus reduced tumor burden through associated cytostatic and anti-angiogenic effects This dual effect of temsirolimus on tumor tissue could contribute to its recently reported efficiency in refractory MCL resistant to conventional chemotherapy Background Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin’s lymphoma (NHL), representing about 6% of NHL cases T(11;14)(q13;q32) chromosomal translocation, one of the most important cytogenetic abnormalities of MCL, juxtaposes genes of cyclin D1 and of immunoglobulin heavy chain, inducing cyclin D1 over-expression and cell cycle deregulation [1] Thus, cyclin D1 over-expression and/or the t(11;14)(q13;q32) translocation are hallmarks of MCL, included in current WHO guidelines for MCL diagnosis [2] MCL patients are usually diagnosed at an advanced stage (III or IV) They become progressively refractory to conventional chemotherapy, and have a poor overall survival [3] Therefore, alternative therapeutic strategies are actively studied The mammalian Target Of Rapamycin (mTOR) is a serine/threonine protein kinase It plays an important * Correspondence: weili_zhao_sih@yahoo.com; anne.janin728@gmail.com Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Inserm, U728, Pôle de Recherches Franco-Chinois, Paris, France Full list of author information is available at the end of the article role in cell growth, protein synthesis, and cell-cycle progression [4] Since mTOR pathway is constitutively activated in MCL, it could be a potent therapeutic target for this disease [5] Recent clinical trials showed that temsirolimus (Wyeth Pharmaceutical, Philadelphia, PA), a mTOR inhibitor, induced a 38% response rate and a prolonged progression-free survival (PFS) of 3.4-6.9 months in refractory MCL patients [6,7] We studied here a refractory MCL patient, who had tumor regression under temsirolimus treatment Case Presentation A 53-year-old male with generalized lymphadenopathy and fatigue, was diagnosed as MCL on inguinal lymph node biopsy After 10 cycles of CHOP and cycles of E-CHOP, lymph nodes bulged Disease was still progressing after cycles of R-ICE Therefore, R-ICE was stopped The patient was recruited in phase III study of temsirolimus (number: 3066K1-305-WW) on August 2006 but was randomized in investigator’s choice group According to the protocol, fludarabine 25 mg/m2 was infused daily for days, and it was repeated every 28 days After cycles, fludarabine had to be stopped © 2010 Wang et al; licensee BioMed Central Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited Wang et al Journal of Hematology & Oncology 2010, 3:30 http://www.jhoonline.org/content/3/1/30 because of severe bone marrow inhibition on March 2007 One year later, enlarged iliac lymph-node compressed ureter, causing renal dysfunction with elevated blood creatinine To confirm the diagnosis of recurrence, a biopsy of enlarged right cervical lymph node was performed and the place was noted on CT scan After confirmation of the MCL recurrence, the patient was permitted to enter the temsirolimus treatment group on March 2008 He received temsirolimus 175 mg/week for weeks, followed by weekly doses of 75 mg Circulation blood count was monitored weekly, CT scan and serum chemistry every other month Temsirolimus was suspended, when absolute neutrophil count